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Updated: May 20, 2025
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages
Alexander Simonis1,2,3, Sebastian J Theobald1,2,3, Anna E Koch2
1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 50937, Germany.
Abstract:
Immune memory plays a critical role in the development of durable antimicrobial immune responses. How precisely mRNA vaccines train innate immune cells to shape protective host defense mechanisms remains unknown. Here we show that SARS-CoV-2 mRNA vaccination significantly establishes histone H3 lysine 27 acetylation (H3K27ac) at promoters of human monocyte-derived macrophages, suggesting epigenetic memory. However, we found that two consecutive vaccinations were required for the persistence of H3K27ac, which matched with pro-inflammatory innate immune-associated transcriptional changes and antigen-mediated cytokine secretion. H3K27ac at promoter regions were preserved for six months and a single mRNA booster vaccine potently restored their levels and release of macrophage-derived cytokines. Interestingly, we found that H3K27ac at promoters is enriched for G-quadruplex DNA secondary structure-forming sequences in macrophage-derived nucleosome-depleted regions, linking epigenetic memory to nucleic acid structure. Collectively, these findings reveal that mRNA vaccines induce a highly dynamic and persistent training of innate immune cells enabling a sustained pro-inflammatory immune response.
Insights
mRNA vaccines train innate immune cells through epigenetic memory, specifically histone H3 lysine 27 acetylation (H3K27ac). This training enhances immune responses and is sustained by booster shots.
Area of Science:
- Immunology
- Epigenetics
- Vaccinology
Background:
- Immune memory is crucial for lasting antimicrobial responses.
- The precise mechanisms by which mRNA vaccines train innate immune cells are not fully understood.
Purpose of the Study:
- To investigate the epigenetic modifications induced by mRNA vaccines in innate immune cells.
- To understand how these modifications contribute to host defense mechanisms and immune memory.
Main Methods:
- Analysis of histone H3 lysine 27 acetylation (H3K27ac) in human monocyte-derived macrophages post-vaccination.
- Assessment of transcriptional changes and cytokine secretion.
- Investigation of the association between H3K27ac and DNA secondary structures.
Main Results:
- SARS-CoV-2 mRNA vaccination established H3K27ac at macrophage promoters, indicating epigenetic memory.
- Two vaccinations were required for persistent H3K27ac, linked to pro-inflammatory responses.
- H3K27ac levels were restored by booster vaccines and associated with G-quadruplex DNA structures.
Conclusions:
- mRNA vaccines induce dynamic and persistent epigenetic training of innate immune cells.
- This training promotes sustained pro-inflammatory immune responses.
- Epigenetic memory in macrophages is linked to nucleic acid structure and vaccine dosage.
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